The isolated perfused collecting tubule of the rabbit will be studied to examine three main physiologic or pathophysiologic issues. Using both electrical and microcalorimetric techniques, the relationship of transepithelial voltage and collecting tubule acidification will be examined under conditions which stimulate or inhibit the generation of a lumen-negative potential difference. Following these studies the effect of lithium, amiloride, ouabain, and urinary tract obstruction on chronic tubular acidification will be studied to test our hypothesis that these agents inhibit acidification secondary to their effect on potential difference. The final group of studies is concerned with the effect of alterations in carbon dioxide tension on collecting tubule acidification. The effect of both chronic and acute alterations of both in vivo and in vitro pCO2 will be studied. Furthermore, the influence of alkali or acid administration on the tubule's response to alterations in pCO2 will be examined. The studies will attempt to determine if chronic hpo- or hypercapnia induces a "memory" effect on in vitro tubular acidification.